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    New Cathepsin Inhibitors to Explore the Fluorophilic Properties of the S2 Pocket of Cathepsin B: Design, Synthesis, and Biological Evaluation

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    5 páginas, 1 figura, 2 tablas -- PAGS nros. 5256-5260Fluor-in or out? Based on β,β-difluorinated cycloaliphatic amino acids, a library of new dipeptide nitriles was evaluated as human cathepsin inhibitors. The orientation of the fluorinated face relative to the protein structure of cathepsin B was elucidated by molecular modeling and NMR studies (see figure). For (R)-configured eutomers, the fluorine atoms are directed to the S2 pocket, whereas in (S)-configured distomers, the fluorinated face is solvent-exposedThis work was supported by a grant from the Ministry of Science and Innovation of Spain (CTQ2007-61462/BQU, CTQ2006-10874-C02-01/BQU, CTQ2009-08536, CTQ2010-19774-C02, and GV/PROMETEO/2010/061). V.R. expresses their thanks for a predoctoral fellowship. C.d.P. and M.S.R thank the same institution for a Ramón y Cajal and a Juan de la Cierva contract, respectively. M.F. is supported by a fellowship from the NRW Forschungsschule Biotech-Pharma, and M.T.S. by a fellowship from the Graduiertenkolleg (GRK) 677 of the Deutsche ForschungsgemeinschaftPeer reviewe
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